Regenerative medicine and cell therapy represent a breakthrough change in paradigm in healthcare compared to more traditional pharmacology approach [1]. The role of proper in vitro protocols and systems for cells and drugs research is vital in creation of cost-effective and scientifically validated treatment methods, at the same time refining, reducing and replacing (“3R”) expensive and scattered animal studies and long expensive clinical trials.
For efficient cell adhesion, proliferation, morphogenesis and differentiation, scaffolds should properly mimic natural in vivo microenvironments and offer local conditions needed for regulation of cellular functions [1,2,3,4]. Besides other factors, the surface and topography of a scaffold affects greatly stem cell specification [3] (for example, a fibrous scaffold was found to increase neural stem cell oligodendrocyte differentiation as well as greatly improve neurite extension and gene expression for neural markers [4]). For example, U.S. Pat. No. 8,148,122 describes flat polymeric, randomly oriented fibers type substrates for cells culturing.
The specific niches with conductive surfaces can promote human mesenchymal stem cells (hMSC) differentiation towards electro-active lineages [3,4,5], opening new scenarios for regeneration of neural, cardiac and similar tissues and capable to assist drug research in vitro. For cells behavior analysis (stem cells proliferation and fate; cancer cells attachment and growth; gene expressions variations, etc.), many properties of 3D scaffolds are essential. For example, substrate stiffness and topology are well known to modulate primary cells shape and morphology with conditions required for further specific differentiation. However, their explicit interactions with cells and extracellular matrix (ECM) system are too complex to allow specific parameters to be separated to a reliable extent.
Many approaches to establish three dimensional (3D) cell culture systems have been undertaken with the major aim to mimic the ECM and configuration and to give structural, dimensional stability to the cells in the culture. Most of them concern gel and collagen systems, polymeric nanofiber scaffolds and porous scaffolds (for example, as shown in U.S. Pat. No. 6,337,198) that intend to promote 3D cell growth [6,7,8]. All of these platforms developed to date, however, have distinct disadvantages such as cell aggregation, low cell survival or experimental limitations. One of the disadvantages is also a high specific response of the cell type to one or another scaffold type, which drives to use many different materials and systems for different cultures making it challenging to compare the results.
The fibrous scaffolds recently gain more attention as they allow more variation in fiber diameter, packing density, porosity, surface state etc. to be tailored for specific needs. For example, US patent application US 20060263417 describes ‘Electrospun blends of natural and synthetic polymer fibers as tissue engineering scaffolds’. Similarly, U.S. Pat. No. 7,704,740 ‘Nanofibrillar structure and applications including cell and tissue culture’ describes the manufacturing of random oriented electrospun nanofibers with the aim to proliferate cell and tissue cultures. However, all these fibers used are made of polymers and produced in random ordering, despite the possibility of their particular arrangement later using different technologies.